Fertility preservation in male adolescents with cancer (2011-2020): A retrospective study in China.

BACKGROUND: According to the studies, more than 80% of pediatric patients with cancer can achieve a survival rate greater than 5 years; however, long-term chemotherapy and/or radiation therapy may seriously affect their reproductive ability. Fertility preservation in adolescents with cancer in China was initiated late, and related research is lacking. Analyze data to understand the current situation and implement measures to improve current practices. METHODS: From 2011 to 2020, data on 275 male adolescents with cancer whose age ranged from 0 to 19 years old were collected from 16 human sperm banks for this retrospective study. Methods include comparing the basic situation of male adolescents with cancer, the distribution of cancer types, and semen quality to analyze the status of fertility preservation. RESULTS: The mean age was 17.39 ± 1.46 years, with 13 cases (4.7%) aged 13-14 years and 262 cases (95.3%) aged 15-19 years. Basic diagnoses included leukemia (55 patients), lymphomas (76), germ cell and gonadal tumors (65), epithelial tumors (37), soft tissue sarcomas (14), osteosarcoma (7), brain tumors (5), and other cancers (16). There are differences in tumor types in different age stages and regions. The tumor type often affects semen quality, while age affects semen volume. Significant differences were found in sperm concentration and progressive motility before and after treatment (p < 0.001). Moreover, 90.5% of patients had sperm in their semen and sperm were frozen successfully in 244 patients (88.7%). CONCLUSIONS: The aim of this study is to raise awareness of fertility preservation in male adolescents with cancer, to advocate for fertility preservation prior to gonadotoxic therapy or other procedures that may impair future fertility, and to improve the fertility status of future patients.

Implementation and evaluation of a fertility preservation telehealth counseling intervention for males with cystic fibrosis.

BACKGROUND: Most males with cystic fibrosis (MwCF) have congenital bilateral absence of the vas deferens and require assisted reproductive technology to conceive, yet many have limited knowledge about how CF affects sexual and reproductive health (SRH). This study evaluates the feasibility, acceptability, and potential effectiveness of telehealth fertility preservation (FP) counseling for MwCF. METHODS: Pre-lung transplant MwCF ≥18 years, recruited from U.S. CF centers, social media, and via snowball sampling, received individualized telehealth counseling. Participants completed intervention feasibility/acceptability one week post-counseling and FP knowledge, care satisfaction, and self-efficacy assessments at baseline and two months post-counseling. We completed acceptability interviews one-week post-counseling and audio-recorded, transcribed, and thematically analyzed results. We descriptively analyzed survey results and conducted pre/post comparisons using paired t-tests. RESULTS: Thirty MwCF (ages 22-49 years) completed counseling. Most were in a relationship (70 %) and White (86.7 %). Telehealth FP counseling was acceptable (M = 4.38/5 ± 0.60), appropriate (M = 4.37/5 ± 0.60), and feasible (M = 4.60/5 ± 0.45) to MwCF. FP knowledge (9.53 vs. 10.40/12; p = .010), care satisfaction (20.23 vs 26.67/32; p<.001), and self-efficacy (22.87 vs 25.20/30; p = .016) improved at two months post-counseling. Despite desiring provider-initiated SRH, wanting children (81 %), and perceiving the CF team as their primary care provider (97 %), 44 % report not receiving information about infertility by the CF team. CONCLUSIONS: Integrating FP counseling into CF care is feasible and acceptable to MwCF and can improve FP knowledge, self-efficacy, and care satisfaction. MwCF desire early and regular provider-initiated SRH education.

Radiation and male reproductive system: Damage and protection.

Male fertility has been declining in recent decades, and a growing body of research points to environmental and lifestyle factors as the cause. The widespread use of radiation technology may result in more people affected by male infertility, as it is well established that radiation can cause reproductive impairment in men. This article provides a review of radiation-induced damage to male reproduction, and the effects of damage mechanisms and pharmacotherapy. It is hoped that this review will contribute to the understanding of the effects of radiation on male reproduction, and provide information for research into drugs that can protect the reproductive health of males.

1-DNJ Alleviates Obesity-Induced Testicular Inflammation in Mice Model by Inhibiting IKKß/ NF-kB Pathway.

Obesity is associated with chronic inflammation that affects various organs in the body, including the reproductive system, which is a key factor in male infertility. 1-Deoxynojirimycin (1-DNJ) is a natural alkaloid in mulberry leaves, which has anti-inflammatory capabilities, yet, it's effects on obesity-induced inflammation-related male infertility remain unclear. Therefore, this research investigates the underlying mechanism by which 1-DNJ may mitigate fertility impairment in male mice caused by obesity-related inflammation. Male mice with high-fat diet (HFD)-induced obesity were treated with 1-DNJ or metformin for 8 weeks. Metabolic profiles were evaluated by enzyme method. Reproductive capacity was assessed by sperm viability, motility and counts, immunohistochemistry was performed to evaluate the testicular damage caused by obesity and inflammation. The inflammation was assessed by measuring the levels of tumor necrosis factor α (TNFα), interleukin 1ß (IL-1ß), and interleukin 6 (IL-6). The activation of IκB kinase ß (IKKß) and nuclear factor κB (NF-κB) was examined using western blot and immunohistochemistry. HFD induced obesity in mice with obvious lipid metabolism disorder. The obese male mice had a decreased testosterone level, impaired sperm motility, and increased inflammatory factors. 1-DNJ treatment improved the testosterone level in the obese mice, ameliorated the testicular structure damage and improve sperm viability. In addition, 1-DNJ treatment inhibited IKKß/NF-kB signaling pathway and reduced inflammation in obese mice. 1-DNJ can improve the fertility of obese men by reducing obesity as well as obesity-induced inflammation. These findings provide new insights for 1-DNJ to alleviate inflammation caused by obesity and provide future possibilities for treating male infertility.

Irritant and repellent behaviors of sterile male Aedes aegypti (L.) (Diptera: Culicidae) mosquitoes are crucial in the development of disease control strategies applying sterile insect technique.

The mosquito Aedes aegypti, known to transmit important arboviral diseases, including dengue, chikungunya, Zika and yellow fever. Given the importance of this disease vector, a number of control programs have been proposed involving the use of the sterile insect technique (SIT). However, the success of this technique hinges on having a good understanding of the biology and behavior of the male mosquito. Behavioral responses of Ae. aegypti male populations developed for SIT technology were tested under laboratory conditions against chemical and natural irritants and repellents using an excito-repellency (ER) chamber. The results showed that there were no significant behavioral escape responses in any of the radiation-sterilized male Ae. aegypti test populations when exposed to citronella, DEET, transfluthrin, and deltamethrin, suggesting that SIT did not suppress the expected irritancy and repellency (avoidance) behaviors. The type of information reported in the current study is vital in defining the effects of SIT on vector behavior and understanding how such behavior may influence the success of SIT technology with regard to other vector control interventions.

Advocating hormonal treatment to prevent adult in-fertility in patients diagnosed with congenital un-descended testes.

In 2007 the Nordic group came to the following unanimous conclusions: In general, hormonal treatment is not recommended, considering the poor immediate results and the possible long-term adverse effects on spermatogenesis. Thus, surgery is to be preferred. However, defective mini puberty inducing insufficient gonadotropin secretion is one of the most common causes of nonobstructive azoospermia in men suffering from congenital isolated unilateral or bilateral cryptorchidism. The extent of alteration in the unilateral undescended testis correlate with the contralateral descended testis, indicating that unilateral cryptorchidism is a bilateral disease. Idiopathic central hypogonadism explains the phenomenon of defective mini puberty in otherwise healthy cryptorchid boys. We therefore recommend hormonal treatment for cryptorchid boys with defective mini puberty. Gonadotropin releasing hormone agonist (GnRHa) treatment following surgery to correct cryptorchidism restores mini puberty via endocrinological and transcriptional effects and prevents adult infertility in most cases. Several genes are important for central hypogonadotropic hypogonadism in mammals, including many that are transcribed in both the brain and testis. At the molecular level, there is no convincing evidence that heat shock is responsible for the observed pathological testicular changes. Thus, impaired transformation of gonocytes is not the result of temperature stress but rather a hormonal imbalance. Cryptorchidism should therefore be considered a serious andrological problem that cannot be successfully treated by early orchidopexy alone.

Protective effects of melatonin against oxidative stress induced by metabolic disorders in the male reproductive system: a systematic review and meta-analysis of rodent models.

Background: Male infertility is a multifaceted issue that has gained scientific interest due to its increasing rate. Studies have demonstrated that oxidative stress is involved in male infertility development. Furthermore, metabolic disorders, including obesity, diabetes, hypo- and hyperthyroidism, are risk factors for male infertility, and oxidative stress is believed to contribute to this association. Melatonin, functioning as an oxidative scavenger, may represent a promising therapeutic approach for the prevention and treatment of metabolic disorder-associated male infertility. Material and methods: We systematically searched three online databases (PubMed, Scopus, and Web of Science) for studies that evaluated the effects of melatonin therapy on metabolic disorders-induce infertility in male rodents. The favorable outcomes were histopathological parameters of testicular tissue, reproductive hormones, and markers of oxidative stress. Then, meta-analyses were done for each outcome. The results are reported as standardized mean difference (Cohen's d) and 95% confidence interval. Results: 24 studies with 31 outcomes were included. Rats and mice were the subjects. Studies have employed obesity, diabetes, hypothyroidism, hyperthyroidism, hyperlipidemia, and food deprivation as metabolic disorders. To induce these disorders, a high-fat diet, high-fructose diet, leptin, streptozotocin, alloxan, carbimazole, and levothyroxine were used. The outcomes included histopathologic characteristics (abnormal sperm morphology, apoptotic cells, apoptotic index, Johnsen's testicular biopsy score, seminiferous epithelial height, tubular basement membrane thickness, tubular diameter, sperm count, and motility), weight-related measurements (absolute epididymis, testis, and body weight, body weight gain, epididymal adipose tissue weight, and relative testis to body weight), hormonal characteristics (androgen receptor expression, serum FSH, LH, and testosterone level), markers of oxidative stress (tissue and serum GPx and MDA activity, tissue CAT, GSH, and SOD activity), and exploratory outcomes (serum HDL, LDL, total cholesterol, triglyceride, and blood glucose level). The overall pooled effect sizes were statistically significant for all histopathological characteristics and some markers of oxidative stress. Conclusions: Melatonin can reduce damage to male rodents' gonadal tissue and improve sperm count, motility, and morphology in metabolic diseases. Future clinical studies and randomized controlled trials are needed to evaluate the safety and effectiveness of melatonin for male infertility in patients with metabolic diseases.

Bioactive compounds as potential alternative treatments to prevent cancer therapy-induced male infertility.

About 8-12% of couples experience infertility, with male infertility being the cause in 50% of cases. Several congenital and acquired conditions, including chronic diseases and their treatments, can contribute to male infertility. Prostate cancer incidence increases annually by roughly 3%, leading to an increment in cancer treatments that have adverse effects on male fertility. To preserve male fertility post-cancer survival, conventional cancer treatments use sperm cryopreservation and hormone stimulation. However, these techniques are invasive, expensive, and unsuitable in prepubertal patients lacking mature sperm cells. Alternatively, nutritional therapies enriched with bioactive compounds are highlighted as non-invasive approaches to prevent male infertility that are easily implementable and cost-effective. In fact, curcumin and resveratrol are two examples of bioactive compounds with chemo-preventive effects at the testicular level. In this article, we summarize and discuss the literature regarding bioactive compounds and their mechanisms in preventing cancer treatment-induced male infertility. This information may lead to novel opportunities for future interventions.

Does severe hypoxia during irradiation of Aedes aegypti pupae improve sterile male performance?

BACKGROUND: The yellow fever mosquito, Aedes aegypti, vectors several pathogens responsible for human diseases. As a result, this mosquito species is a priority for control by mosquito control districts in Florida. With insecticide resistance development becoming a concern, alternative control strategies are needed for Ae. aegypti. Sterile insect technique (SIT) is an increasingly popular option that is being explored as a practical area-wide control method. However, questions about sterile male performance persist. The objectives of this study were to determine the extent to which hypoxia exposure prior to and during irradiation effects the longevity, activity and mating competitiveness of sterile male Ae. aegypti. METHODS: Male longevity was monitored and analyzed using Cox regression. Mosquito activity was recorded by an infrared beam sensor rig that detected movement. Competing models were created to analyze movement data. Fecundity and fertility were measured in females mated with individual males by treatment and analyzed using one-way ANOVAs. Mating competition studies were performed to compare both hypoxia and normoxia treated sterile males to fertile males. Competitiveness of groups was compared using Fried's competitiveness index. RESULTS: First, we found that subjecting Ae. aegypti pupae to 1 h of severe hypoxia (< 1 kPa O2) did not directly increase mortality. One hour of hypoxia was found to prevent decreases in longevity of irradiated males compared to males irradiated in normoxic conditions. Exposure to hypoxia prior to irradiation did not significantly improve activity of sterile males except at the highest doses of radiation. Hypoxia did significantly increase the required dose of radiation to achieve > 95% male sterility compared to males irradiated under normoxic conditions. Males sterilized after an hour in hypoxic conditions were significantly more competitive against fertile males compared to males irradiated under normoxic conditions despite requiring a higher dose of radiation to achieve sterility. CONCLUSIONS: Hypoxia was found to greatly improve key performance metrics in sterile male Ae. aegypti without any significant drawbacks. Little work other than increasing the target dose for sterility needs to be conducted to incorporate hypoxia into SIT programs. These results suggest that SIT programs should consider including hypoxia in their sterile male production workflow.

The effects and molecular mechanism of heat stress on spermatogenesis and the mitigation measures.

Under normal conditions, to achieve optimal spermatogenesis, the temperature of the testes should be 2-6 °C lower than body temperature. Cryptorchidism is one of the common pathogenic factors of male infertility. The increase of testicular temperature in male cryptorchidism patients leads to the disorder of body regulation and balance, induces the oxidative stress response of germ cells, destroys the integrity of sperm DNA, yields morphologically abnormal sperm, and leads to excessive apoptosis of germ cells. These physiological changes in the body can reduce sperm fertility and lead to male infertility. This paper describes the factors causing testicular heat stress, including lifestyle and behavioral factors, occupational and environmental factors (external factors), and clinical factors caused by pathological conditions (internal factors). Studies have shown that wearing tight pants or an inappropriate posture when sitting for a long time in daily life, and an increase in ambient temperature caused by different seasons or in different areas, can cause an increase in testicular temperature, induces testicular oxidative stress response, and reduce male fertility. The occurrence of cryptorchidism causes pathological changes within the testis and sperm, such as increased germ cell apoptosis, DNA damage in sperm cells, changes in gene expression, increase in chromosome aneuploidy, and changes in Na+/K+-ATPase activity, etc. At the end of the article, we list some substances that can relieve oxidative stress in tissues, such as trigonelline, melatonin, R. apetalus, and angelica powder. These substances can protect testicular tissue and relieve the damage caused by excessive oxidative stress.

Resveratrol benefits on sperm DNA, chromatin structure and reproductive outcomes of varicocelized rats.

In varicocele, the main cause of sperm DNA damage is oxidative stress (OS). Resveratrol, a polyphenol with antioxidant properties, can protect cells from injuries caused by OS. We investigated the benefits of resveratrol against reproductive damage caused by experimental varicocele induced from peripuberty. Eighty peripubertal male rats were distributed into 4 groups: sham-control (S), varicocele (V), resveratrol (R) and varicocele treated with resveratrol (VR). Varicocele was induced through the partial ligature of the left renal vein. Resveratrol was given in a daily dose of 300 mg/kg body weight (gavage). Sperm samples were collected at 100 days of age for vitality, DNA fragmentation and chromatin protamination evaluations. OS analyses were carried out. Rats from all groups were mated with healthy primiparous females for evaluation of reproductive capacity and embryonic quality. The V group showed reduction of sperm vitality, altered chromatin protamination and sperm DNA integrity and high levels of OS. The VR group showed an improvement of oxidative status, sperm vitality, DNA integrity and chromatin structure, and an enhancement in the gestational index and embryonic quality. Therefore, we showed in this experimental model that resveratrol is a promising nutraceutical adjuvant and should be deeply studied to mitigate subfertility in varicocele.

Role of HPV vaccination for prevention of male infertility.

Infertility is an important health problem affecting about 16% of couples worldwide and male infertility is responsible for about 50% of the cases. Among the causes, sexually transmittable infections (STI) are widely accepted by researchers as etiological factors of male infertility and their incidence is growing. In detail, several reports documented the presence of HPV in semen from infertile patients. In these cases, HPV DNA was bound to the sperm surface and played a role in the infertility by affecting many sperm parameters. Despite a safe and highly effective vaccine is currently available to prevent HPV infection, there are still no effective treatments to completely clear the virus. However, recent studies highlighted that HPV vaccination can be an effective tool to counteract HPV seminal infection even in already infected patients. In fact, it seems able to reduce the viral time to clearance and the relapse of infection in males with persistence of HPV in semen. In this review, we aimed to explore, in a narrative way, currently available literature about HPV infection of male genital tract and the mechanisms by which HPV virions may alter sperm parameters and, therefore, male fertility, both natural and assisted. Moreover, we aimed to report and discuss the most recent evidence about the role of HPV vaccine administration as a therapeutic tool in males with persistent HPV seminal infection.

Mediterranean Diet as a Shield against Male Infertility and Cancer Risk Induced by Environmental Pollutants: A Focus on Flavonoids.

The role of environmental factors in influencing health status is well documented. Heavy metals, polycyclic aromatic hydrocarbons (PAHs), polychlorinated biphenyls, dioxins, pesticides, ultrafine particles, produced by human activities put a strain on the body's entire defense system. Therefore, together with public health measures, evidence-based individual resilience measures are necessary to mitigate cancer risk under environmental stress and to prevent reproductive dysfunction and non-communicable diseases; this is especially relevant for workers occupationally exposed to pollutants and/or populations residing in highly polluted areas. The Mediterranean diet is characterized by a high intake of fruits and vegetables rich in flavonoids, that can promote the elimination of pollutants in tissues and fluids and/or mitigate their effects through different mechanisms. In this review, we collected evidence from pre-clinical and clinical studies showing that the impairment of male fertility and gonadal development, as well as cancers of reproductive system, due to the exposure of organic and inorganic pollutants, may be counteracted by flavonoids.

Curcumin nanocrystals attenuate cyclophosphamide-induced testicular toxicity in mice.

The cancer therapy using cyclophosphamide (CP) has been associated with adverse effects on the testicular function that raises concerns about the future fertility potential among cancer survivors. Curcumin, a polyphenol, has shown to possess a plethora of biological functions including tissue protective effects. In the present study, we investigated the protective effects of curcumin nanocrystals (NC) in mitigation of CP-induced testicular toxicity. Healthy adult (8-10 week) and prepubertal (2 week) male Swiss albino mice were injected with a single dose of CP (200 mg/kg) intraperitoneally (i.p). NC (4 mg/kg, i.p.) was administered every alternate day, for 35 days in adult mice while, a single dose of NC was injected intraperitoneally to prepubertal mice 1 h prior to CP. Administration of multiple doses of NC ameliorated CP-induced testicular toxicity in adult mice, which was evident from the improved sperm functional competence, sperm chromatin condensation, seminiferous tubule architecture and decreased apoptosis in testicular cells. Further, administration of NC 1 h prior to CP in prepubertal mice modulated the expression of genes pertaining to proliferation, pluripotency, DNA damage and DNA repair in spermatogonial cells at 24 h after the treatment. Overall, these results suggest that NC could be a promising chemoprotective agent, which can have potential application in male fertility preservation.

How can fertility counseling be implemented for every newly diagnosed pediatric patient facing gonadotoxic treatment?-A single-center experience.

Since the survival rates of pediatric patients undergoing cancer treatment or hematopoietic stem cell transplantation (HSCT) have increased rapidly in recent decades, the late effects of treatment are now an important focus of patient care. Access to fertility preservation (FP) procedures as well as their financing differs considerably across Europe. However, some countries in Europe have recently changed the legal basis for financing FP procedures; therefore, the implementation of structures is mandatory to give patients access to FP. In this prospective cohort study, we characterized the process for establishing pediatric fertility counseling, including the development of an in-house standard procedure for recommendations regarding FP with potentially gonadotoxic treatment and valuating data from all FP counseling sessions. All data concerning patient characteristics (pubertal status, disease group) and recommendation of FP measures were prospectively collected and adoption of FP measures analyzed. Prior to the establishment of a structured process for FP in our pediatric oncology and stem cell transplantation center, there was no standardized FP counseling. We demonstrate that with the establishment of an inhouse standard procedure, it is possible to give consistent yet individualized FP counseling to approximately 90% of our patients facing gonadotoxic treatment, counseling over 200 patients between 2017 and 2019. This pilot study could potentially be adapted in other pediatric hematology, oncology, and stem cell transplantation centers to allow a more standardized handling of FP counseling for all patients facing gonadotoxic treatment.

Antioxidant and cytoprotective effects of Nigella sativa L. seeds on the testis of monosodium glutamate challenged rats.

Monosodium glutamate (MSG) is one of the most widely spread food additives that might cause male infertility. However, Nigella sativa L. seeds (NSS) could provide a solution. This study was designed to investigate the potential effects of NSS on rats ingesting MSG. To achieve this aim, adult male albino rats were randomly equally assigned into three groups for 21 days: control group received no treatment, MSG group received MSG as 30 g/kg feed, and MSG + NSS group received MSG as 30 g/kg and NSS as 30 g/kg feed. Testis histomorphometry showed marked deterioration by MSG as atrophic seminiferous tubules with degeneration of their lining cells, damaged Leydig cells and decreased germ cells number. Periodic Acid Schiff stain indicated irregular interrupted basement membranes. Glutathione reductase, superoxide dismutase 2 (SOD2), and caspase-3 immuno-expressions increased in testicular cells. Testosterone levels were significantly decreased in MSG challenged rats along with significant increase in luteinizing hormone levels, whereas NSS normalized this hormonal profile. MSG exposure also caused significantly increased lipid peroxides (LPO), glutathione-S-transferase, and total antioxidant capacity (TAC) whereas nitric oxide and SOD2 were significantly decreased. NSS succeeded in rebalance LPO and TAC and ameliorated the histoarchitectural disturbances. NSS mitigated MSG-induced testicular impairment by its antioxidant and cytoprotective activities.

Fertility preservation in men: a contemporary overview and a look toward emerging technologies.

Cancer and oncologic therapies can have significant adverse effects on male reproductive potential, leaving many men permanently infertile. Fertility preservation has emerged as a key survivorship issue over the past 20 years, and numerous professional societies have published guidelines calling for fertility preservation to become a routine component of oncologic care. Most males with cancer are able to produce a semen specimen for fertility preservation, but numerous other methods of sperm procurement are available for patients who cannot provide a sufficient sample. Despite these options, fertility preservation will remain a challenge for prepubertal boys and men without sperm production. For these patients, experimental and investigational approaches offer the hope that one day they will translate to the clinical arena, offering additional pathways for successful fertility preservation care.